The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Crohn's disease (CD) is a disease of diverse clinical phenotypes and patients with complicated disease phenotypes such as those with stricturing and/or internal penetrating disease behaviors often require surgical intervention. Over a 10 year period, approximately 80% of patients can expect to develop a complication and close to 50% of CD patients will progress to surgery (1, 2). This is in contrast to the small percentage of patients presenting with a complication, and requiring surgery at time of diagnosis. One of the biggest challenges facing clinicians today is predicting which patients will progress to complication resulting in intestinal resection. The identification of these “rapidly progressive” patients early in the course of their disease may assist in the decision regarding the early introduction of effective intervention strategies and customizing therapies based on risk of underlying disease. Those at highest risk of disease complication may well benefit most from early use of immunomodulators and/or biologic therapies. Despite major advances in genome discovery, there have only been a few studies that have considered the role of genetics in determining disease behavior. Variation in NOD2/CARD15 has been shown to be associated with stricturing CD, need for surgery as well as surgical recurrence (13-18). Serological immune markers have been shown to predict more aggressive disease. Recent genome-wide association (GWA) studies have identified multiple IBD susceptibility loci although their phenotypic consequences remain unknown. The ability to identify patients with Crohn's disease (CD) who are at highest risk for rapid progression to surgery would be invaluable in guiding initial therapeutic choices.